Childhood-onset epilepsy appeared to speed up brain ageing by about 10 years, a found a small prospective study in Finland over more than 50 years.
Over about 55 years of follow-up, people with childhood-onset epilepsy had greater rates of cognitive changes and more amyloid plaques, reported Dr Matti Sillanpää of the University of Turku in Finland, and colleagues, at the American Epilepsy Society annual meeting held in Chicago and online this week (3-7 December 2021).
Signs of brain ageing were more advanced in people with focal than generalised epilepsy and in people with active epilepsy. No participant had dementia.
“Various aspects of cognitive and brain ageing processes can be abnormal in persons with uncomplicated childhood-onset epilepsies as they enter their 60s, even for those whose epilepsy remitted many years ago,” co- author Bruce Hermann, PhD, of University of Wisconsin Medical School in Madison, told MedPage Today.
“As some clinical and brain changes were found to be associated with health and lifestyle factors, such as hypertension, education, and lifetime drug load, greater attention to treatable factors earlier in life may benefit patients as they age.”
The researchers compared 51 people with childhood-onset epilepsy with 52 matched controls without epilepsy, evaluating them in 2012 and 2017. Retention over the five-year interval was 80% for the epilepsy group and 88% for controls, leaving 41 and 46 people in each group, respectively, in 2017.
Participants were diagnosed with childhood-onset epilepsy at about age five, and mean age of people in the epilepsy group at follow-up was about 63. Amyloid was assessed by 11C-Pittsburgh compound B (PIB) PET.
A total of 32 people in the epilepsy group were in remission for 10 years or more; nine people had active epilepsy that persisted for decades.
Neurologic signs were significantly more common in people with childhood epilepsy not in remission (P=0.015), with cerebellar signs the most frequent abnormality (P<0.001). Neurologic signs in general (P=0.008) and cerebellar signs in particular (P=0.018) were more common in focal than in generalised epilepsy.
In 2012, 22% of people with childhood-onset epilepsy had amyloid plaques versus 7% of controls. By 2017, those percentages increased to 33% and 11%, respectively. There was no difference in the presence of amyloid plaques among people with active epilepsy compared with people in remission.
In the five-year interval from 2012 to 2017, using a common threshold of meaningful cognitive change (z < -1.5) corrected for demographics and practice, the childhood-onset epilepsy group showed significant (P<0.05) prospective declines versus controls on measures of verbal reasoning, immediate recall, and set-shifting.
People with active epilepsy showed additional significant (P<0.05) adverse declines in delayed memory and object naming, compared with controls and with people in remission.
Peripheral neuropathy occurred particularly in people with active epilepsy who had a higher lifetime phenytoin (Dilantin) load. MRI hippocampal atrophy in people with childhood-onset epilepsy was associated with arterial hypertension (P=0.017). MRI white matter abnormalities were linked with an absence of vocational education (P=0.011).
“Our results suggest it is important for those with childhood-onset epilepsy to work to achieve seizure control but it’s also vital that they pay attention to risk and resilience factors for healthy brain and cognitive aging, including a healthy diet, exercise, and social activity, as well as treating high blood pressure, high cholesterol, and high blood glucose levels," Hermann said.
“We do not know yet if people with childhood-onset epilepsy who have amyloid plaques are more likely to develop Alzheimer’s disease, a critical question we will be studying in the future,” he added.
Study details
Brain Aging in Childhood-Onset Epilepsy: A Prospective Population-Based Study
Matti Sillanpää, Bruce Hermann, Juha Rinne, Riitta Parkkola, Maiju Saarinen, Mira Karrasch, Jani Saunavaara, Eero Rissanen, Petri Tiitta, Kevin Dabbs, Juho Joutsa, Shlomo Shinnar.
Presented at the American Epilepsy Society annual meeting on 5 December 2021
Rationale
To determine the course of brain and cognitive ageing in a population-based cohort of participants with uncomplicated childhood-onset epilepsy (COE) and controls, followed over five decades, with focus on a recent five-year (2012-2017) prospective in-person assessment of clinical, cognitive and neuroimaging status.
Methods
The cohort consisted of 51 ageing participants with COE and their 52 matched controls who underwent detailed in-person prospective neurologic, neuropsychological and neuroimaging (structure, diffusion, amyloid deposition) assessments in 2012 followed by reassessment in 2017 to characterize interval change and the relation of identified changes to clinical epilepsy status (remitted vs. active epilepsy) and health and lifestyle factors. Retention over the 5-year interval was 80% for COE and 88% for controls (41 COE and 40 control participants). Participants were examined neurologically, cognitively (language, memory, executive function, speed), MRI was evaluated clinically and via Freesurfer vertex analyses, and brain amyloid uptake was assessed by PET 11C-Pittsburgh compound B [PIB] ligand evaluated visually by a consensus of two experienced clinical investigators.
Results
At follow-up the mean age of the COE participants was 63.2 years (SD 4.14, range 55.8–70.6) and 63.0 years (SD 4.13, range 56.0–69.9) for controls. Neurologic signs were significantly more common in COE participants not in remission (p=0.015) with cerebellar signs the most frequent abnormality (p < 0.001). Neurologic signs in general (p=0.008) and cerebellar signs in particular (p=0.018) were significantly more common in focal than in generalised epilepsies. Peripheral neuropathy occurred particularly in subjects with active epilepsy with higher lifetime phenytoin load. MRI white matter abnormalities were significantly associated with absence of vocational education (p=0.011), and MRI hippocampal atrophy in COE subjects associated with arterial hypertension (p=0.017). In the combined study cohort of COE subjects and controls, presenting neurologic signs increased both in the subjects and controls from the 2012 to 2017 study. Regarding five-year interval cognitive course using a common threshold of meaningful cognitive change (z < – 1.5) corrected for demographics and practice, the COE group showed significant (p < 0.05) prospective declines versus controls on measures of verbal reasoning, immediate recall and set-shifting. COE participants with active epilepsy showed additional significant (p < 0.05) adverse declines compared to controls and COE participants with remitted epilepsy in delayed memory and object naming. Regarding amyloid imaging, in 2012 22% of COE participants and 7% of controls were PIB positive (p=0.03). In 2017, 33% of the COE compared to 11% of controls were PIB positive (p=0.04).
Conclusions
Clinical, cognitive and neuroimaging findings show brain aging trajectories that are more accelerated in COE participants with active adult childhood-onset epilepsy, and particularly in focal epilepsy. In terms of brain amyloid accumulation, subjects with childhood epilepsy appear approximately 10 years advanced in brain ageing compared to matched controls.
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